Li Guowei, Wei Xiaohua, Lv Kai, Xie Dongna, Liu Mei, Xu Yi, Ma Dong, Jiao Genlong
The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, China.
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Carbohydr Polym. 2025 Jul 1;359:123578. doi: 10.1016/j.carbpol.2025.123578. Epub 2025 Apr 9.
MRSA-induced arthritis is a prevalent and highly debilitating orthopedic condition. The inflammatory response induced by bacterial infection hinders tissue repair and exacerbates bone loss. Traditional antibiotic therapies are limited by low bioavailability, substantial side effects, and narrow efficacy, rendering them inadequate for comprehensive treatment of arthritis. Nitric oxide (NO) has demonstrated considerable potential in overcoming bacterial resistance, modulating immune responses, and facilitating tissue repair. Therefore, a stage-specific NO release strategy, tailored to the distinct phases of bacterial arthritis, is essential for effective treatment. In this study, mesoporous polydopamine nanoparticles were utilized as NO donors (mPDA/NONOate) and encapsulated within a supramolecular hydrogel formed via the host-guest interaction between α-cyclodextrin (α-CD) and Pluronic F127. The injectable nature of the resulting NO/PDA-Gel hydrogel ensured uniform distribution within irregular bone joint infection sites, minimizing NO donor loss and enhancing local bioavailability. Notably, upon near-infrared (NIR) irradiation, the hydrogel induces a rapid increase in local temperature, facilitating rapid NO release. At the same time, the synergistic photothermal effect effectively kills bacteria and rapidly controls the infection. Without light irradiation, NO is sustainably and stably released from the NO/PDA-Gel, modulating the bone immune microenvironment, alleviating inflammation, promoting chondrocyte proliferation and differentiation, and accelerating bone tissue repair, thus significantly shortening the healing time of MRSA-induced arthritis. In conclusion, the injectable self-assembled NO/PDA-Gel offers a precise, stage-matched therapeutic approach for MRSA-induced arthritis and holds promise for the treatment of deep-seated infections caused by other multidrug-resistant pathogens.
耐甲氧西林金黄色葡萄球菌（MRSA）引起的关节炎是一种常见且极具致残性的骨科疾病。细菌感染引发的炎症反应会阻碍组织修复并加剧骨质流失。传统抗生素疗法存在生物利用度低、副作用大以及疗效范围窄等局限性，不足以对关节炎进行全面治疗。一氧化氮（NO）在克服细菌耐药性、调节免疫反应以及促进组织修复方面已展现出巨大潜力。因此，针对细菌性关节炎不同阶段量身定制的阶段特异性NO释放策略对于有效治疗至关重要。在本研究中，介孔聚多巴胺纳米颗粒被用作NO供体（mPDA/NONOate），并封装在通过α-环糊精（α-CD）与普朗尼克F127之间的主客体相互作用形成的超分子水凝胶中。所得的NO/PDA-凝胶水凝胶的可注射性确保了其在不规则骨关节感染部位的均匀分布，最大限度地减少了NO供体的损失并提高了局部生物利用度。值得注意的是，在近红外（NIR）照射下，水凝胶会使局部温度迅速升高，从而促进NO的快速释放。与此同时，协同光热效应可有效杀灭细菌并迅速控制感染。在无光照的情况下，NO从NO/PDA-凝胶中持续稳定释放，调节骨免疫微环境，减轻炎症，促进软骨细胞增殖和分化，并加速骨组织修复，从而显著缩短MRSA引起的关节炎的愈合时间。总之，可注射的自组装NO/PDA-凝胶为MRSA引起的关节炎提供了一种精确的、阶段匹配的治疗方法，并有望用于治疗由其他多重耐药病原体引起的深部感染。
